The activation of STAT3 then initiates downstream proliferative and anti-apoptotic pathways involving G protein-coupled receptors (GPCRs) and Toll-like receptors (TLRs), as well as interleukin-6 (IL-6) and its familial members, ultimately leading to trastuzumab resistance in HER2-positive breast tumors (21, 35, 36). This evidence concerns the gene ERBB2 and breast neoplasm.